> Meanwhile, evolving resistance also comes at a cost. We don’t know that directly, but we can infer it pretty well. If resistance to tetrodotoxin were cheap and easy, everything would evolve it. [..] We don’t know, but we’re pretty sure there must be something. We know that garter snakes outside of the Pacific Northwest are much less resistant to tetrodotoxin. They’ll drop dead from doses that their Oregon cousins simply ignore. So evolving the resistance must have some cost or drawback.
I'm not so sure that's really the case; it's more that for many animals there simply isn't any pressure to evolve (or retain) this trait.
It's not like the natural selection process has a feature list it can tick off. It operates with zero foresight and an incredibly dumb principle: whatever helps procreation.
Cows are not dying due to tetrodotoxin poisoning in significant numbers, as far as I know, so there is no reason for them to evolve resistance to it. The same applies to most animals, including the snakes outside that area.
Your dog can synthesise their own vitamin C and will never develop scurvy. Most animals can do this – humans and some other primates are the exception. An ancestor lost the trait for vitamin C synthesis by chance, and because these primates were living in trees eating lots of fruit with vitamin C, evolution simply didn't notice. There is no disadvantage to being able to synthesise vitamin C, and no advantage in dropping the trait. It didn't affect procreation (at the time). Now we're all stuck with it.
Now, maybe all of this does have a cost for the snakes. But it's far from a given that there is one.
I think it might be more useful to look at the author's claim from the other side of the lense. We do carry around barely useful traits, like resistance to toxins that we seldom come in contact with. We can assume that carrying such traits is cheap. If resistance to tetrodotoxin was one such cheap trait, it might have been more prevalent, but it's not so, it could be inferred that it's expensive. Or at least, not cheap.
This is another case of a huge fallacy humans seem endlessly afflicted with: The Root Cause Fallacy.
You are assuming there is but one cause for development and/or loss of resistance.
There may not be much pressure to develop resistance to tetrodotoxin for most species. Simultaneously there might be a higher metabolic cost to retaining it for some species but not for others. It is also possible that resistance with low cost is very rarely lost which is why we carry resistance to toxins we don't often see but population bottlenecks in ancestral lines can cause loss of a trait to propagate - even by accident. And much like Vitamin C loss if it doesn't matter the loss sticks. We should not forget that there are multiple resistance mechanisms as well: an immune system generally primed to fight certain common causes of mortality can, entirely by accident, also be primed to recognize and destroy certain proteins conferring resistance to some toxins and not others.
I have barely scratched the surface above. The random walk of evolution and its constant hoarding tendencies should make everyone skeptical simplistic mechanisms of action as well as "just so" explanations of evolutionary history.
FWIW most things are multi-causal. I previously made the same argument about house prices. People who claim it is caused by foreign money, low interest rates, restrictive zoning, etc all want their pet theory to be The One True Reason. In reality the market is complex and many of the proposed causes are merely contributing factors.
That resistance to toxins we don't encounter often enough to constitute selective pressure, we carry around only if it's the accidental byproduct of another selected-for trait. Otherwise entropy would take care of it, sooner or later. Parent is right, evolution doesn't pay an annual subscription fee for some service which was useful in the past and might come in handy in the future.
It’s not some binary thing but degrees of adaptation.
People can handle significantly more of a wide range of plant toxins like theobromine and caffeine (both found in chocolate) which harm more pure predators like dogs in very low doses, but where rare for out imitate ancestors.
Cattle, deer etc however can handle many of those at much higher doses.
> like resistance to toxins that we seldom come in contact with.
Is that because resistance to those toxins was strongly selected for in humans, or because the source of those toxins did not strongly select for effectiveness in humans?
Not wrong, but one could frame that as a "cost" that you pay in the space of genealogical problem solving. Having one less constraint makes it easier to adapt to other evolutionary pressures
I omitted some bits from the quote for brevity and HN's faux-quoting sucks, but that's not really the type of "cost" the article is talking about: "maybe they’re suffering from much more subtle neurological effects, like being prone to insomnia or hallucinations or sexual dysfunction. Or maybe they’re just a bit dim."
That claim jumped out to me as well. Evolution is supply and demand, cost and benefit, capacity and constraints, none of it balanced by anything apart from luck.
This is categorically false, we know evolving bigger brains required us to reduce our muscle mass compared to other primates, for the energy budget required to create such brains.
> An ancestor lost the trait for vitamin C synthesis by chance, and because these primates were living in trees eating lots of fruit with vitamin C, evolution simply didn't notice. There is no disadvantage to being able to synthesise vitamin C, and no advantage in dropping the trait.
The fact that guinea pigs, fruit bats, and passerines (almost half of all bird species!) also have a mutated GULO gene suggests that there is in fact some pressure to get rid of it as soon as it is bioavailable from diet.
> There is no disadvantage to being able to synthesise vitamin C, and no advantage in dropping the trait.
So why did the trait of that mutant primate spread throughout the entire population? There should instead be a mixture of those who can and those who can’t synthesize vitamin C.
(Indeed, one should perhaps not so blithely assume that there was sufficient fruit for everyone and so C didn’t matter… for it is precisely the ability to survive in times of drought and scarcity that drive evolution, and there id no reason to suspect a population that could synthesize their own vitamin C was less fit than a population that couldn’t. The issue of vitamin C is far from simple…)
There is no reason for it to spread, but also no reason for it not to. Presumably there was another (completely unrelated) trait, and it happened to spread because of that.
> There should instead be a mixture of those who can and those who can’t synthesize vitamin C.
Probably was for a long time. All of this happened about 60 millions years ago. It's been a while.
> There is no disadvantage to being able to synthesise vitamin C,
Synthesizing vitamin C takes energy, energy that could be used for other biological processes. It's also possible excess vitamin C has some minor deleterious effect. For example, it's an antioxidant, and these render immune cells somewhat less effective against certain threats (which they use oxidizing chemicals to destroy). It's been found larger doses of the ACE vitamins causes increased growth of lung cancer, probably due to reduced immune attack.
Some have argued against this idea, though, although I'm not convinced by the argument (see if you can spot the problem.)
Survivorship bias, you perceive it doesn't come with a cost, but perhaps some species that were exposed to it died from it because they failed to adapt because it does come with a cost they couldn't pay, so they went extinct, like it's wildly common.
Reptilian Predation squeezed mamalian reproduction into the fast and the furious . Meanwhile birds and turtles reproduce hapoy at methusalem ages. No creator, no design, just merciless pressure that stupidly rewards successful maiming to adapt.
But a nonzero number of animals and people die of tetrodoxin poisoning, so there is some pressure. Therefore if it were cheap and easy enough, it’s likely we all would have evolved it. That cheapness threshold might just be incredibly high.
Well, there is some "cause-and-effect" in evolution.
Whenever a species winds up isolated in a cave, it loses eyesight really quickly in evolutionary terms because making and maintaining an eye is so metabolically expensive. So, while the mutations are random, any of them that can save the energy of developing vision get selected for very quickly.
So, even though the mutations are random, it really looks like "cause-and-effect" from the outside: get isolated in cave->lose vision; get exposed to outside light again->regain vision.
By the same token, changes that aren't very expensive metabolically will have very weak "cause-and-effect" because there is no particular pressure to carry the mutations forward or clean them up.
No need to be annoyed. I think if you look deeper, you might find that, in fact, all occurrences of what we call cause and effect are of a similar nature.
Water lillies not only are not dangerous, they’re partially edible and have also been used in medicines. Do you mean peace lilly or calla lilly? Neither is deadly, but they can make you ill. Water hemlock is deadly and has white flowers?
I recently learned that (Wikipedia) "Vascular cambia are found in all seed plants except for five angiosperm lineages which have independently lost it; Nymphaeales, Ceratophyllum, Nelumbo, Podostemaceae, and monocots.[1]" Four of these lineages are aquatic plants (including water lilies) and some scientists theorize monocots may have also evolved in the water. I seem to recall reading that aquatic plants don't "need" woody growth for structural stability, but can't find a source right now.
Interestingly written article. Raises some questions:
>Newts with weaker poison? They get eaten. Snakes with less resistance? Have trouble finding newts they can choke down, and don’t get to steal their poison. So the arms race continues.
How does a snake know that the Newt has weaker/strong poison? Is it leaving some Newts along and eating others, or is it eating any Newt it runs across? Does a strong-poison newt survive snake consumption attempts?
Maybe a better way to frame it is over time, there's some genetic sequence that gave the snake a preference for eating this newt in particular out of all potential prey and some other genetic sequence that gives them a bit of resistance so they can store the poison inside them. Those snakes that eat more of them with that genetic makeup, up to a point, are better able to reproduce. Run a few thousand years of iterations over this process, where the snake and newt are in a red queen situation, both running faster and faster just to keep up. It is possible to look at this as situation where neither the snake or newt is conscious of the choices or there is no ability to make decision, there is only following the built in behavior.
I think the preceding sentence in that paragraph answers it. Important context here is that garter snakes tend to swallow prey whole. tldr: a strongly poisoned newt survives consumption attempts.
> And it explains why the newts keep evolving to be more toxic: the snake may want to eat newts generally, but if an individual newt packs enough of a wallop, the snake may just retch it up and go after a different one. Newts with weaker poison? They get eaten. Snakes with less resistance? Have trouble finding newts they can choke down, and don’t get to steal their poison. So the arms race continues.
> Snakes with less resistance? Have trouble finding newts they can choke down, and don’t get to steal their poison.
That's got to be an extremely weak effect. No snake gets an individual benefit from eating the newts. They get a collective benefit, that predators recognize the species as poisonous, in which all snakes, poisonous and delicious alike, share equally.
The problem is large enough that actually-poisonous animals routinely have delicious mimics of entirely different species who free-ride off of the work the originals do to be poisonous.
You can't explain why snakes apparently need to avoid sending a dishonest signal with a theory that predicts that mimics don't exist.
I found this on Wikipedia, but tldr they taste test it.
> Successful predation of the rough-skinned newt by the common garter snake is made possible by the ability of individuals in a common garter snake population to gauge whether the newt's level of toxin is too high to feed on. T. sirtalis assays toxin levels of the rough-skinned newt and decides whether or not the levels are manageable by partially swallowing the newt, and either swallowing or releasing the newt.
> Turns out there is an answer: the garter snakes sequester the tetrodotoxin, storing it in their livers. This makes them toxic to their own predators.
This might be a total tangent, but every time I see “newts”, I think about how Karel Capek actually coined the word robot in his 1920 play R.U.R., and then later gave us War with the Newts...really smart amphibians.
Thanks for sharing.
I can understand why. You rarely see newts mentioned, even though they’re biologically fascinating. Maybe it’s just because people mistake them for another kind of lizard.
I did several semesters' worth of biology fieldwork in college that involved handling many of these guys, under the guidance of a professor who was obsessed with them. Their toxicity was discussed more as a point of interest rather than an immediate danger. We always wore gloves when handling them, but the rationale was more for the newts' protection rather than our own. I never heard of there being a newt poisoning incident during the past decades of this professor overseeing similar fieldwork. Of course, eating them was out of the question.
Yes, I must have played with these newts at least a couple dozen times as a child, they were under every leaf and log in the forest and near streams where I grew up.
> It’s so toxic that the poison from a single newt can easily kill several adult humans. You could literally die from licking this newt, just once.
TBF there is one death reported in Oregon from someone eating an entire newt in 1979, but they aren’t as bad as the article would have you believe. Many of us have handled these newts. There would be a lot more dead people if licking is all it took.
> A 29-year-old man drank approximately 150 mL of whiskey at about 11 AM July 9, 1979. At 6 PM he swallowed a 20-cm newt on a dare. Within ten minutes he complained of tingling of the lips. During the next two hours he began complaining of numbness and weakness and stated that he thought he was going to die. He refused to be transported to a hospital and was left alone for 15 minutes and then experienced cardiopulmonary arrest
Readit News
I'm not so sure that's really the case; it's more that for many animals there simply isn't any pressure to evolve (or retain) this trait.
It's not like the natural selection process has a feature list it can tick off. It operates with zero foresight and an incredibly dumb principle: whatever helps procreation.
Cows are not dying due to tetrodotoxin poisoning in significant numbers, as far as I know, so there is no reason for them to evolve resistance to it. The same applies to most animals, including the snakes outside that area.
Your dog can synthesise their own vitamin C and will never develop scurvy. Most animals can do this – humans and some other primates are the exception. An ancestor lost the trait for vitamin C synthesis by chance, and because these primates were living in trees eating lots of fruit with vitamin C, evolution simply didn't notice. There is no disadvantage to being able to synthesise vitamin C, and no advantage in dropping the trait. It didn't affect procreation (at the time). Now we're all stuck with it.
Now, maybe all of this does have a cost for the snakes. But it's far from a given that there is one.
You are assuming there is but one cause for development and/or loss of resistance.
There may not be much pressure to develop resistance to tetrodotoxin for most species. Simultaneously there might be a higher metabolic cost to retaining it for some species but not for others. It is also possible that resistance with low cost is very rarely lost which is why we carry resistance to toxins we don't often see but population bottlenecks in ancestral lines can cause loss of a trait to propagate - even by accident. And much like Vitamin C loss if it doesn't matter the loss sticks. We should not forget that there are multiple resistance mechanisms as well: an immune system generally primed to fight certain common causes of mortality can, entirely by accident, also be primed to recognize and destroy certain proteins conferring resistance to some toxins and not others.
I have barely scratched the surface above. The random walk of evolution and its constant hoarding tendencies should make everyone skeptical simplistic mechanisms of action as well as "just so" explanations of evolutionary history.
FWIW most things are multi-causal. I previously made the same argument about house prices. People who claim it is caused by foreign money, low interest rates, restrictive zoning, etc all want their pet theory to be The One True Reason. In reality the market is complex and many of the proposed causes are merely contributing factors.
People can handle significantly more of a wide range of plant toxins like theobromine and caffeine (both found in chocolate) which harm more pure predators like dogs in very low doses, but where rare for out imitate ancestors.
Cattle, deer etc however can handle many of those at much higher doses.
Is that because resistance to those toxins was strongly selected for in humans, or because the source of those toxins did not strongly select for effectiveness in humans?
The fact that guinea pigs, fruit bats, and passerines (almost half of all bird species!) also have a mutated GULO gene suggests that there is in fact some pressure to get rid of it as soon as it is bioavailable from diet.
So why did the trait of that mutant primate spread throughout the entire population? There should instead be a mixture of those who can and those who can’t synthesize vitamin C.
(Indeed, one should perhaps not so blithely assume that there was sufficient fruit for everyone and so C didn’t matter… for it is precisely the ability to survive in times of drought and scarcity that drive evolution, and there id no reason to suspect a population that could synthesize their own vitamin C was less fit than a population that couldn’t. The issue of vitamin C is far from simple…)
> There should instead be a mixture of those who can and those who can’t synthesize vitamin C.
Probably was for a long time. All of this happened about 60 millions years ago. It's been a while.
Synthesizing vitamin C takes energy, energy that could be used for other biological processes. It's also possible excess vitamin C has some minor deleterious effect. For example, it's an antioxidant, and these render immune cells somewhat less effective against certain threats (which they use oxidizing chemicals to destroy). It's been found larger doses of the ACE vitamins causes increased growth of lung cancer, probably due to reduced immune attack.
Some have argued against this idea, though, although I'm not convinced by the argument (see if you can spot the problem.)
https://pmc.ncbi.nlm.nih.gov/articles/PMC3145266/
Has anybody modeled what percent of a population has to die from something for the protective gene to become widespread?
Whenever a species winds up isolated in a cave, it loses eyesight really quickly in evolutionary terms because making and maintaining an eye is so metabolically expensive. So, while the mutations are random, any of them that can save the energy of developing vision get selected for very quickly.
So, even though the mutations are random, it really looks like "cause-and-effect" from the outside: get isolated in cave->lose vision; get exposed to outside light again->regain vision.
By the same token, changes that aren't very expensive metabolically will have very weak "cause-and-effect" because there is no particular pressure to carry the mutations forward or clean them up.
Dead Comment
Turns out, it's the water-lily.
https://crookedtimber.org/2025/03/14/occasional-paper-the-in...
>Newts with weaker poison? They get eaten. Snakes with less resistance? Have trouble finding newts they can choke down, and don’t get to steal their poison. So the arms race continues.
How does a snake know that the Newt has weaker/strong poison? Is it leaving some Newts along and eating others, or is it eating any Newt it runs across? Does a strong-poison newt survive snake consumption attempts?
> And it explains why the newts keep evolving to be more toxic: the snake may want to eat newts generally, but if an individual newt packs enough of a wallop, the snake may just retch it up and go after a different one. Newts with weaker poison? They get eaten. Snakes with less resistance? Have trouble finding newts they can choke down, and don’t get to steal their poison. So the arms race continues.
That's got to be an extremely weak effect. No snake gets an individual benefit from eating the newts. They get a collective benefit, that predators recognize the species as poisonous, in which all snakes, poisonous and delicious alike, share equally.
The problem is large enough that actually-poisonous animals routinely have delicious mimics of entirely different species who free-ride off of the work the originals do to be poisonous.
You can't explain why snakes apparently need to avoid sending a dishonest signal with a theory that predicts that mimics don't exist.
> Successful predation of the rough-skinned newt by the common garter snake is made possible by the ability of individuals in a common garter snake population to gauge whether the newt's level of toxin is too high to feed on. T. sirtalis assays toxin levels of the rough-skinned newt and decides whether or not the levels are manageable by partially swallowing the newt, and either swallowing or releasing the newt.
Deleted Comment
Second-order effects are so cool
This might be a total tangent, but every time I see “newts”, I think about how Karel Capek actually coined the word robot in his 1920 play R.U.R., and then later gave us War with the Newts...really smart amphibians. Thanks for sharing.
[0]https://www.discovermagazine.com/planet-earth/a-beautiful-we...
> It’s so toxic that the poison from a single newt can easily kill several adult humans. You could literally die from licking this newt, just once.
TBF there is one death reported in Oregon from someone eating an entire newt in 1979, but they aren’t as bad as the article would have you believe. Many of us have handled these newts. There would be a lot more dead people if licking is all it took.
> A 29-year-old man drank approximately 150 mL of whiskey at about 11 AM July 9, 1979. At 6 PM he swallowed a 20-cm newt on a dare. Within ten minutes he complained of tingling of the lips. During the next two hours he began complaining of numbness and weakness and stated that he thought he was going to die. He refused to be transported to a hospital and was left alone for 15 minutes and then experienced cardiopulmonary arrest